TY - JOUR
T1 - Effect of azelnidipine and amlodipine on single cell mechanics in mouse cardiomyocytes
AU - Iribe, Gentaro
AU - Kaihara, Keiko
AU - Ito, Hiroshi
AU - Naruse, Keiji
N1 - Funding Information:
This work was supported by the Japan Society for the Promotion of Science (JSPS KAKENHI : 23300167 , 22136008 , 22240056 ) and Daiichi Sankyo Co., Ltd .
PY - 2013
Y1 - 2013
N2 - Azelnidipine and amlodipine are dihydropyridine-type Ca2+ channel blockers for the treatment of hypertension. Although these drugs have high vasoselectivity and small negative inotropic effects in vivo, little is known regarding their direct effects on cellular contractility without humoral regulation or the additive effects of these drugs with other antihypertensive drugs on myocardial contractility. To investigate the effects of Ca2+ channel blockers on single cell mechanics, mouse cardiomyocytes were enzymatically isolated, and a pair of carbon fibers was attached to opposite cell-ends to stretch the cells. Cells were paced at 4 Hz superfused in normal Tyrode solution at 37 1C. Cell length and active/passive force calculated from carbon fiber bending were recorded in 6 different preload conditions. Slopes of end-systolic force - length relation curves (maximum elastance) were measured as an index of contractility before and after drugs were administered. Azelnidipine at 10 nM and 100 nM did not change maximum elastance, while amlodipine at 100 nM did decrease maximum elastance. The combination of RNH-6270 (active form of angiotensin II receptor blocker, olmesartan, 10 nM) and either amlodipine (10 nM) or azelnidipine (10 nM) did not affect maximum elastance. Although both amlodipine and azelnidipine can be used safely at therapeutically relevant concentrations even in combination with olmesartan, the present results suggest that azelnidipine has a less negative inotropic action compared to amlodipine.
AB - Azelnidipine and amlodipine are dihydropyridine-type Ca2+ channel blockers for the treatment of hypertension. Although these drugs have high vasoselectivity and small negative inotropic effects in vivo, little is known regarding their direct effects on cellular contractility without humoral regulation or the additive effects of these drugs with other antihypertensive drugs on myocardial contractility. To investigate the effects of Ca2+ channel blockers on single cell mechanics, mouse cardiomyocytes were enzymatically isolated, and a pair of carbon fibers was attached to opposite cell-ends to stretch the cells. Cells were paced at 4 Hz superfused in normal Tyrode solution at 37 1C. Cell length and active/passive force calculated from carbon fiber bending were recorded in 6 different preload conditions. Slopes of end-systolic force - length relation curves (maximum elastance) were measured as an index of contractility before and after drugs were administered. Azelnidipine at 10 nM and 100 nM did not change maximum elastance, while amlodipine at 100 nM did decrease maximum elastance. The combination of RNH-6270 (active form of angiotensin II receptor blocker, olmesartan, 10 nM) and either amlodipine (10 nM) or azelnidipine (10 nM) did not affect maximum elastance. Although both amlodipine and azelnidipine can be used safely at therapeutically relevant concentrations even in combination with olmesartan, the present results suggest that azelnidipine has a less negative inotropic action compared to amlodipine.
KW - Carbon fiber
KW - Force - length relation
KW - Maximum elastance
KW - Stretch
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U2 - 10.1016/j.ejphar.2013.05.030
DO - 10.1016/j.ejphar.2013.05.030
M3 - Article
C2 - 23747592
AN - SCOPUS:84885482220
VL - 715
SP - 142
EP - 146
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -